We propose to investigate the fundamental issue of whether histone gene expression is controlled at the transcriptional level in the mammalian cell cycle. The system we will use is a chinese hamster fibroblast cell line (K12), which when incubated at 35 degree C, can be induced to progress synchronously through the cell cycle. However, when the cells are incubated at 40.5 degree C, a temperature sensitive mutation will block the cells at the mid-point of Gl phase. Using a cloned, homologous probe for the histone gene H3, we will measure the rate of transcription, the steady state concentration and the turn over rates of its mRNA throughout the cell cycle. The effect of the ts mutationon histone mRNA concentration and turn over rates will also be studied. In addition, we plan to examine the size of the hamster histone H3 mRNA(s) and determine if pre-cursors exist. We will isolate genomic fragments containing the H3 genes and orientate the coding sequences within the cloned sequences. This will provide information for future experiments to map the histone transcriptional units. The long term goal of this research is to unravel the molecular control mechanisms which must be exerted on animal cells to govern the differential expression of the histone genes during the cell cycle.